Multicenter analysis of diaphragm pacing in tetraplegics with cardiac pacemakers: positive implications for ventilator weaning in intensive care units.

BACKGROUND: Diaphragm pacing (DP) can replace mechanical ventilation in tetraplegics and in trials has assisted respiration in amyotrophic lateral sclerosis patients. This report describes results of DP in patients with cardiac pacemakers. METHODS: Prospective, single-center and multicenter, nonrandomized, controlled, interventional protocols under U.S. Food and Drug Administration and/or institutional review board approval were evaluated. Patients underwent laparoscopic diaphragm motor point mapping to identify optimal electrode site for implantation. With diaphragm conditioning, patients were weaned from their ventilator. Perioperative and long-term assessments between the cardiac pacemakers and DP were analyzed for any device-to-device interactions. RESULTS: Over 300 subjects were implanted from 2000 to 2010. Twenty tetraplegics with cardiac pacemakers and DP were analyzed from 6 sites. Subjects ranged from 19 to 61 years old with DP implantation 6 months to 24 years postinjury. There were no immediate or long-term device to device interactions. All patients achieved diaphragm-paced tidal volumes exceeding their basal requirements and, after conditioning, all patients could go >4 hours without mechanical ventilators; 71% could go 24 hours continuously. CONCLUSION: DP can be safely implanted in tetraplegics having cardiac pacemakers. Applications for temporary use of DP to maintain diaphragm type 1 muscle fiber and improve posterior lobe ventilation may benefit complex critical care patients.

Hyperthermia-induced heat shock activates the transcription factor c/EBP-beta and augments IL-6 production in human intestinal epithelial cells.

BACKGROUND: Interleukin (IL)-6 production is increased in gut mucosa during sepsis and endotoxemia. The heat shock response augments IL-6 production under these conditions, but the mechanism is not known. We hypothesized that heat shock stimulates IL-6 production in enterocytes by increasing expression and activity of the transcription factor C/EBB. STUDY DESIGN: Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43 degrees C for 1 hour). Other cells were kept at 37 degrees C. Cells were then treated with 0.5 ng/mL human recombinant IL-1beta for 4 hours. C/EBP-beta and delta DNA binding activity was determined by electrophoretic mobility shift assay and supershift analysis. In additional experiments, Caco-2 cells were transfected with expression plasmids for C/EBP-beta and delta, after which cells were subjected to hyperthermia and treatment with IL-1beta. RESULTS: C/EBP-beta, but not delta, protein levels and DNA binding activity were increased in Caco-2 cells expressing the heat shock response. Induction of the heat shock response augmented IL-6 production in IL-1beta-treated cells overexpressing C/EBP-beta, but not delta. CONCLUSIONS: Increased IL-6 production in IL-1beta-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of CIEBP-beta. Because recent studies suggest that IL-6 might be an antiinflammatory cytokine and might exert protective effects in gut mucosa and enterocytes, understanding mechanisms by which the heat shock response augments IL-6 production might have important clinical implications.

The stress response decreases NF-kappaB activation in liver of endotoxemic mice.

Recent studies suggest that the stress (heat shock) response protects cells and tissues from inflammatory and other noxious insults. The transcription factor nuclear factor-kappa B (NF-kappaB), normally sequestered in the cytoplasm by its inhibitory protein IkappaB, regulates many genes involved in the inflammatory response to critical illness. Endotoxemia is associated with increased NF-kappaB activity in liver but the effect of the stress response on endotoxin-induced NF-kappaB activation in the liver is not known. We hypothesized that the stress response inhibits NF-kappaB DNA binding activity in liver during endotoxemia. The stress response was induced in mice by hyperthermia (42 degrees C for 3 min) or sodium arsenite (10 mg/kg) and resulted in increased hepatic heat shock protein-72 levels. After induction of the stress response, mice were injected subcutaneously with endotoxin (12.5 mg/kg) or a corresponding volume of sterile saline. NF-kappaB DNA binding activity in the nuclear fraction of liver tissue increased and cytoplasmic IkappaB-alpha levels decreased after endotoxin injection, with a maximal effect seen at 60 min. The endotoxin-induced increase in NF-kappaB DNA binding activity and decrease in IkappaB-alpha levels were inhibited by prior induction of the stress response. In additional experiments, treatment of mice with sodium arsenite after induction of endotoxemia blunted the increase in NF-kappaB activity, indicating a therapeutic potential of sodium arsenite, in addition to its preventive effect. The present results suggest that the protective effects of the stress response in vivo may, at least in part, be due to inhibited NF-kappaB activation.